Elbasvir/Grazoprevir has performed well in clinical trials, even among patients with HIV and other coinfections.
A new review of clinical trial data show the combination therapy elbasvir/grazoprevir (EBR/GR) has high rates of efficacy for patients with genotypes 1a, 1b, and 4 chronic hepatitis C (HCV) infection.
The US Food and Drug Administration (FDA) approved the fixed-dose oral therapy, which is sold under the brand name Zepatier, back in 2016. The new review, by a team of Japanese researchers, explores the mechanisms behind the drug’s clinical efficacy, as well as some of its limitations.
“The fixed-dose once-daily oral combination regimen of EBR/GZR has beneficial effects in antiviral treatment for HCV [genotype] 1- and 4-infected [treatment-naive] and [treatment-experience] patients, with or without compensated cirrhosis, HIV coinfection, or advanced [chronic kidney disease],” wrote lead author Kenichi Morikawa, MD, PhD, of the Hokkaido University Graduate School of Medicine.
Elbasvir is an HCV nonstructural protein 5A inhibitor, while grazoprevir is an NS3/4A protease inhibitor. In the C-EDGE Trial of treatment-naive patients, EBR/GZR achieved sustained virological response at 12 weeks (SVR12) in 92% of patients. In that trial, 23% of patients had compensated cirrhosis, but that did not appear to affect whether or not a patient achieved SVR12.
Meanwhile, in the C-EDGE Coinfection trial, treatment-naive patients who were infected with genotype 1a HCV and also with HIV achieved SVR12 status 97% of the time. Among patients with genotype 1b HCV, the figure was 95%. But investigators noted that patients with baseline NS5A polymorphisms at certain amino acid positions experienced lower rates of efficacy.
Notably, resistance associated substitutions (RASs) did not appear to have a significant impact on efficacy.
“Despite the fact that baseline NS3 RASs were commonly observed, a 12-week regimen of EBR/GZR demonstrated high SVR12 rates among patients infected with Gt 1a, 1b, or 4,” Morikawa and colleagues wrote.
The EDGE-TE trial, in which 34% of patients had compensated cirrhosis, showed that among patients with genotype 1a, EBR/GZR had an SVR12 rate of 92% without ribavirin and 93% when given in tandem with ribavirin. At 16 weeks, 94% of the non-ribavirin group had SVR12, but 100% of the ribavirin group achieved SVR.
Meanwhile, patients with the 1b genotype achieved SVR12 at a rate of 100% after 12 weeks without ribavirin and 97% with ribavirin. After 16 weeks, 98% achieved SVR12 without ribavirin and 100% achieved the endpoint with ribavirin.
Regarding chronic kidney disease (CKD), the C-SURFER study found 94% of patients with CKD achieved SVR 12 after taking EBR/GZR. Half of the patients in the study had genotype 1a HCV and the other half had genotype 1b HCV. About three-fourths (76%) of the patients in the study were hemodialysis patients.
The authors noted a few limitations of EBR/GZR.
“Limitations of EBR/GZR are the occurrence of potential concomitant drug—drug interactions, the absence of pangenotypic efficacy, the need for baseline evaluation of RASs in Gt 1a-infected patients, and the putative hepatotoxicity of protease inhibitors in Child–Pugh B and C cirrhosis in a minority of clinical situations,” Morikawa and colleagues wrote.
The study, “Safety and efficacy of elbasvir/grazoprevir for the treatment of chronic hepatitis C: current evidence” was published online in Drug Design, Development and Therapy.